EP1945341A1 - Stabilized dry compositions, method for obtaining them and use thereof - Google Patents

Stabilized dry compositions, method for obtaining them and use thereof

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Publication number
EP1945341A1
EP1945341A1 EP06831040A EP06831040A EP1945341A1 EP 1945341 A1 EP1945341 A1 EP 1945341A1 EP 06831040 A EP06831040 A EP 06831040A EP 06831040 A EP06831040 A EP 06831040A EP 1945341 A1 EP1945341 A1 EP 1945341A1
Authority
EP
European Patent Office
Prior art keywords
composition according
dry composition
particle size
stabilized dry
particles
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP06831040A
Other languages
German (de)
French (fr)
Other versions
EP1945341B1 (en
Inventor
Guy Derrieu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Virbac SA
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Virbac SA
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Application filed by Virbac SA filed Critical Virbac SA
Publication of EP1945341A1 publication Critical patent/EP1945341A1/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/20—Agglomerating; Granulating; Tabletting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the invention relates to stabilized dry compositions comprising at least one active principle, their processes for obtaining them, as well as their uses.
  • Pulverulent products and, more particularly, food compositions or medicaments, presented in dry powder form, are known to bulk. This change in physical state, in addition to preventing the marketing and use of the product, leads to chemical degradations that affect the effectiveness of the composition and can also be dangerous during its use. This caking, also called caking, is mainly induced by the presence of water.
  • this water is due to several factors. First of all, it is due to the nature of the packaging which, according to its intrinsic structure, has a certain porosity to gases and, consequently, to water vapor. Then, it is due to the very small presence in the composition of water related to the molecular structure, water of crystallization and / or absorption water or relative humidity.
  • the caking is very strongly influenced by external factors such as temperature or humidity and, more certainly, by their combination.
  • patent document EP 1 382 245 discloses in particular an anti-caking method for agricultural active ingredients by adding an inorganic substance of silica type.
  • patent document US 2003/0074940 discloses a combination of adjuvants composed of fertilizer granules coated with a reducing agent and optionally an anti-caking agent.
  • the solution of the invention to this problem has the first object a stabilized dry composition, comprising at least one active ingredient, consisting of a powdery portion of average particle size between 1 and 250 microns, characterized in that it incorporates anti-caking particles whose average particle size is between 200 and 1500 ⁇ m and is at least 2.5 times greater than the average particle size of said powdery part.
  • Its second object is a process for producing a stabilized dry composition, comprising at least one active principle, consisting of a powdery part with an average particle size of between 1 and 250 ⁇ m, characterized in that it comprises the step of mixing said powdery portion with anti-caking particles having an average particle size of 200 to 1500 ⁇ m and is at least 2.5 times greater than the average particle size of said powdery portion.
  • compositions as defined above as food, dietary supplement or drug packaged in different forms.
  • a composition comprises both a powdery portion with a particle size of between 1 and 250 ⁇ m and anti-caking particles whose mean particle size is between 200 and 1500 ⁇ m and is at least 2.5 times greater than the grain size distribution. average of the powdery part, it does not take in mass and does not undergo any physical or chemical modification.
  • the stabilized dry composition according to the invention comprises at least one active principle and is constituted a powdery part and anti-clumping particles which are distinguished mainly by their particle size.
  • the pulverulent part according to the invention is in the form of a fine powder composed of dry particles, at least on their surface.
  • said powder has an average particle size of between 1 and 250 ⁇ m and more preferably between 10 and 100 ⁇ m.
  • the pulverulent portion of the composition is present in concentrations ranging preferably from 40% to 95% by weight relative to the total weight of the composition.
  • the powdery part consists of active ingredients, excipients or a mixture of both.
  • the average particle size of the active ingredients and excipients will be approximately identical.
  • excipient or the mixture of excipients capable of entering into the formulation of the pulverulent part of the composition according to the invention are chosen from sugars such as lactose, sucrose, dextrose or maltodextrins, inorganic salts such as that dicalcium phosphate or calcium carbonate, organic acids and their salts such as citric acid, sodium acetate or potassium propionate, vegetable flours and their by-products such as wheat flour, its, rice starch or gluten corn, or their mixture.
  • sugars such as lactose, sucrose, dextrose or maltodextrins
  • inorganic salts such as that dicalcium phosphate or calcium carbonate
  • organic acids and their salts such as citric acid, sodium acetate or potassium propionate
  • vegetable flours and their by-products such as wheat flour, its, rice starch or gluten corn, or their mixture.
  • the pulverulent part consists solely of active principles.
  • the anti-clumping particles of the invention are also dry, at least on their surface, and are often in a spherical, ovoid or elongated form. Their surface is smooth, porous and / or hollow, in a regular or irregular manner.
  • the anti-caking particles have a particle size ranging from 200 to 1500 ⁇ m, more preferably from 250 to 800 ⁇ m, and even more preferentially from 300 to 700 ⁇ m.
  • the anti-clumping particles of the composition according to the invention consist of active principles, excipients or a mixture of the two.
  • the active ingredients are included, partially or totally, in the anti-clumping particles of the composition according to the invention.
  • the excipient or the mixture of excipients capable of entering into the composition of the anti-clumping particles of the composition according to the invention are identical to the excipient or to the mixture of excipients used in the composition of the powdery part. .
  • the anticaking particles of the composition according to the invention are simple or complex bodies used in the manufacture or preparation of a food or drug composition. These are in particular particles of sugars, mixtures of saccharides, organic acids and their salts, polyols, inorganic salts or hollow particles based on at least one acrylic or methacrylic polymer or copolymer, taken alone. or in mixture.
  • sugars advantageously choose lactose or sucrose.
  • saccharide mixtures the dextrates will advantageously be chosen.
  • the citric acid will advantageously be chosen.
  • mannitol or sorbitol will advantageously be chosen.
  • inorganic salts the hydrated calcium phosphate is advantageously chosen.
  • hollow particles based on at least one acrylic or methacrylic polymer or copolymer the polymethacrylate particles will advantageously be chosen.
  • Such anti-clumping particles may advantageously be obtained by granulation and consequently be in the form of granules.
  • Such granulation can be carried out by mixing in a humid medium, and include drying and then calibration steps. It can also be carried out in a fluidized air bed or on devices known from the state of the art combining a set of operations leading to the desired particles, by compacting, by granulation or by coating.
  • the anticaking particles are present in concentrations ranging preferably from 5 to 60% by weight relative to the total weight of the composition and, more preferably, from 10 to 40%.
  • the active ingredient according to the invention is defined as any simple or complex body having an activity of any nature on its environment. It comes by definition to oppose an excipient which, simple or complex, has no activity on the environment or, on the active principle (s).
  • the active principles according to the invention are simple or complex bodies chosen from vitamins, minerals, trace elements, amino acids, proteins, enzymes, growth powders, plant powders or extracts thereof, insect growth inhibitors, anti-bacterials, antifungals, antiseptics, antibiotics, antibiomimetics, antiparasitic agents and / or synthetic anti-infectives, taken alone or as a mixture.
  • the stabilized dry composition according to the invention is a food, a food supplement or a drug.
  • Food supplements are products intended to be ingested as supplements of the current diet, in order to compensate for the actual or supposed insufficiency of the daily contributions. They contribute to the good functioning of the organism and to the good restoration of the balance of the different functions which animate it when these are disturbed.
  • These dietary supplements may be in the form of nutraceuticals that are products made from food products, but made available as a tablet, powder, potion or other medicinal forms usually not associated with food.
  • composition according to the invention may further comprise, in its powdery portion and / or in the anti-caking particles, conventional pharmaceutically acceptable adjuvants known to those skilled in the art or food additives such as preservatives, antioxidants, acidifying agents, acid correctors, anti-foaming agents, emulsifiers, flavorings, flavoring agents, flavor enhancers, foaming agents, gelling agents, humectants, sequestering agents, stabilizers and thickeners.
  • conventional pharmaceutically acceptable adjuvants known to those skilled in the art or food additives such as preservatives, antioxidants, acidifying agents, acid correctors, anti-foaming agents, emulsifiers, flavorings, flavoring agents, flavor enhancers, foaming agents, gelling agents, humectants, sequestering agents, stabilizers and thickeners.
  • the composition according to the invention results for example from a simple mechanical mixture of a powdery part containing active ingredients and anti-caking particles as described above.
  • it preferably comprises between 40 and 95% w / w (weight of the total weight of the composition) of the powdery part and between 5 and 60% w / w of anti-caking particles, and more preferably between 60 and 90% wt. / m of active ingredients in powder form and between 10 and 40% m / m of anti-caking particles.
  • the pulverulent portion has a mean particle size of between 20 and 100 ⁇ m and the anti-caking particles have an average particle size of between 200 and 800 ⁇ m and at least 2.5 times greater than the average particle size of the powdery part.
  • the average particle size of the anti-caking particles is at least 4 times greater than the average particle size of the powdery part.
  • composition according to the invention is dry, that is to say not or slightly impregnated with liquid and, in particular water. It preferably has a water activity of less than 0.4 and, more preferably, a water activity of less than 0.3.
  • compositions according to the invention have an expiry date much greater than the expiry date that could have been obtained in pulverulent dry compositions of the state of the art, preserved under the same conditions.
  • the process for preparing a stabilized dry composition according to the invention is characterized in that it comprises the following step of mixing the part pulverulent medium particle size with an average particle size of between 200 and 1500 microns and is at least 2.5 times greater than the average particle size of said active ingredient.
  • This step of mixing the pulverulent part with anti-caking particles is carried out according to the usual known techniques.
  • the preparation process is carried out under controlled humidity conditions ensuring a water activity of less than 0.4 in the composition obtained.
  • the invention also relates to the use of the composition according to the invention as a food, as a food supplement, or as a medicament.
  • composition according to the invention is in a powder form, used in the state or to be packaged in different forms according to the subsequent applications. It can advantageously be used for the manufacture of medicaments for human or veterinary use, which are preferably in the form of capsules or capsules, possibly gastroresistant, hard-coated or soft.
  • the medicament advantageously comprises an excipient or a filler element so as to form a premelange in the form of a powder.
  • the excipient or the mixture of excipients used to form said premix are identical to those present in the powdery part of the composition according to the invention.
  • Example 1 Pulverulent composition containing plant extracts and its preparation. Constituents Content (% m / m)
  • composition is prepared by mixing the active ingredients in pulverulent form with an average particle size of about 50 ⁇ m (plant extracts absorbed on maltodextrins) with anhydrous citric acid particles.
  • Vitamins A, D 3 , E and K 3 Vitamin B mixture (feed grade) 23, 00
  • Mannitol particles 17, 00 The composition is prepared by mixing the active ingredients in powder form of average particle size of about 50 microns (mixture of amino acids and vitamins) with mannitol particles of 250 to 800 microns.
  • composition is prepared in four phases: Phase 1: mannitol (76.70%), crospovidone (3.10%) and monocrystalline cellulose (6.2%) are granulated in the presence of an aqueous-alcoholic solution of povidone (14%). Phase 2: the mannitol particles obtained are dried and then calibrated so that their mean diameter is between 250 ⁇ m and 800 ⁇ m.
  • Phase 3 the mannitol particles are mixed with the active ingredients in pulverulent form.
  • Phase 4 the composition obtained is then packaged in welded aluminized bags.
  • composition A composition A
  • composition B comprising the same components as composition A, but in which the citric acid particles have been replaced by citric acid powder of a small particle size (close to 25 microns).
  • compositions A and B are given below:
  • compositions A and B are placed in an oven maintained at a temperature of temperature of 40 ° C. and in the presence of 75% humidity.
  • the physical aspect of the compositions is analyzed each month.
  • composition A does not have a setting in mass contrary to composition B.
  • composition B with citric acid particles having a particle size of between 300 .mu.m and 700 .mu.m (composition A) has the effect of suppressing the setting of mass and thus improve the stability of the composition according to the invention.
  • composition A kept at temperatures of the order of 25 0 C, should have a significantly improved shelf life over substantially non-particulate compositions.

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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Vaporization, Distillation, Condensation, Sublimation, And Cold Traps (AREA)

Abstract

Stabilized dry composition comprises an ingredient having a powdery portion of 1-25 mu m and anticaking particles of 200-1500 mu m, which is at least 2.5 times greater in the particle size of the powdery portion. Independent claims are included for: (1) the preparation of the composition comprising mixing the ingredient and the anticaking particles; and (2) a medicament comprising the composition.

Description

COMPOSITIONS SECHES STABILISEES, LEURS PROCEDES D'OBTENTION ET LEURS UTILISATIONS STABILIZED DRY COMPOSITIONS, PROCESSES FOR THEIR PREPARATION AND USES THEREOF
L'invention concerne des compositions sèches stabilisées comprenant au moins un principe actif, leurs procédés d'obtention, ainsi que leurs utilisations.The invention relates to stabilized dry compositions comprising at least one active principle, their processes for obtaining them, as well as their uses.
Les produits pulvérulents et, plus particulièrement, les compositions alimentaires ou les médicaments, présentés sous forme sèche en poudre, sont connus pour prendre en masse. Ce changement d'état physique, outre le fait d'empêcher la commercialisation et l'utilisation du produit, conduit à des dégradations chimiques qui nuisent à l'efficacité de la composition et peuvent également être dangereuses lors de son utilisation. Cette prise en masse, appelée également mottage, est principalement induite par la présence d'eau.Pulverulent products and, more particularly, food compositions or medicaments, presented in dry powder form, are known to bulk. This change in physical state, in addition to preventing the marketing and use of the product, leads to chemical degradations that affect the effectiveness of the composition and can also be dangerous during its use. This caking, also called caking, is mainly induced by the presence of water.
La présence de cette eau est due à plusieurs facteurs. Tout d'abord, elle est due à la nature de l'emballage qui, selon sa structure intrinsèque, présente une certaine porosité aux gaz et, par suite, à la vapeur d'eau. Ensuite, elle est due à la présence même infime, dans la composition, d'eau liée à la structure moléculaire, d'eau de cristallisation et/ou d'eau d'absorption ou humidité relative.The presence of this water is due to several factors. First of all, it is due to the nature of the packaging which, according to its intrinsic structure, has a certain porosity to gases and, consequently, to water vapor. Then, it is due to the very small presence in the composition of water related to the molecular structure, water of crystallization and / or absorption water or relative humidity.
Bien entendu, le mottage est très fortement influencé par des facteurs extérieurs comme la température ou l'humidité et, plus certainement, par leur combinaison.Of course, the caking is very strongly influenced by external factors such as temperature or humidity and, more certainly, by their combination.
On a cherché à développer de nouveaux moyens pour lutter contre le phénomène de mottage, notamment en développant des procédés d'enrobage ou de granulation de poudre, en ajoutant, à la composition, des poudres poreuses ou absorbant l'eau telle que la poudre d'amidon ou la poudre d'anhydride silicique, ou alors, par la mise au point d'emballages de plus en plus performants. Si la mise en œuvre de procédés d'enrobage et de granulation semble répondre à la problématique de la présente invention, ces opérations s'avèrent être relativement complexes, longues et onéreuses. En outre, chaque application constitue un cas particulier. Ainsi, l'adjuvant d'enrobage ou de granulation est spécifique de la composition, de même que le procédé de fabrication. En pratique, cela est nécessaire pour éviter d'engendrer toutes actions négatives pour les actifs de la composition. Par ailleurs, l'adjonction de poudre poreuse ou absorbant l'eau est largement utilisée mais elle montre vite des limites en n'empêchant pas la prise en masse des compositions sèches pulvérulentes.It has been sought to develop new means for combating the caking phenomenon, in particular by developing processes for coating or granulating powder, by adding to the composition, porous or water-absorbing powders such as duststream powder. starch or silicic anhydride powder, or else, by the development of more and more efficient packaging. If the implementation of coating and granulation processes seems to answer the problem of the present invention, these operations prove to be relatively complex, time consuming and expensive. In addition, each application is a special case. Thus, the coating or granulation adjuvant is specific to the composition, as is the manufacturing process. In practice, this is necessary to avoid generating any negative actions for the assets of the composition. Furthermore, the addition of porous or water-absorbing powder is widely used, but it quickly shows limits by not preventing the setting of powdery dry compositions.
On se référera notamment aux documents de l'état de la technique suivants. Tout d'abord, le document brevet EP 1 382 245 divulgue notamment une méthode d'anti- mottage pour des principes actifs agricoles par ajout d'une substance inorganique de type silice. Ensuite, le document brevet US 2003/0074940, décrit une combinaison d'adjuvants composée de granules d'engrais enrobés par un agent réducteur et éventuellement un agent antimottant.Reference will be made in particular to the following documents of the prior art. Firstly, patent document EP 1 382 245 discloses in particular an anti-caking method for agricultural active ingredients by adding an inorganic substance of silica type. Next, patent document US 2003/0074940 discloses a combination of adjuvants composed of fertilizer granules coated with a reducing agent and optionally an anti-caking agent.
On notera enfin, l'enseignement du document brevet US 2005/0003043, qui divulgue une méthode d' anti-mottage de produits protéiques. Cette méthode consiste à ajouter au moins un agent réducteur et un chaotrope, composé qui dénature les protéines, à la composition protéique. Toutefois, la déshydratation et la dénaturation de composés peut entraîner une accélération de leur dégradation mais aussi modifier leur solubilité. Compte tenu de ce qui précède, un problème que se propose de résoudre l'invention est de réaliser des compositions sèches stabilisées, comprenant au moins un principe actif, qui ne présentent pas de prise en masse lors de leur conservation. La solution de l'invention à ce problème posé a pour premier objet une composition sèche stabilisée, comprenant au moins un principe actif, constituée d'une partie pulvérulente de granulométrie moyenne comprise entre 1 et 250 μm, caractérisée en ce qu'elle incorpore des particules antimottantes dont la granulométrie moyenne est comprise entre 200 et 1500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne de ladite partie pulvérulente . Elle a pour second objet un procédé de fabrication d'une composition sèche stabilisée, comprenant au moins un principe actif, constituée d'une partie pulvérulente de granulométrie moyenne comprise entre 1 et 250 μm, caractérisé en ce qu'il comporte l'étape de mélange de ladite partie pulvérulente avec des particules antimottantes dont la granulométrie moyenne est comprise entre 200 et 1500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne de ladite partie pulvérulente .Finally, note the teaching of the patent document US 2005/0003043, which discloses a method of anti-caking of protein products. This method consists in adding at least one reducing agent and a chaotropic compound which denatures the proteins to the protein composition. However, the dehydration and the denaturation of compounds can accelerate their degradation but also modify their solubility. In view of the foregoing, a problem to be solved by the invention is to produce stabilized dry compositions, comprising at least one active ingredient, which do not exhibit a setting in mass during their storage. The solution of the invention to this problem has the first object a stabilized dry composition, comprising at least one active ingredient, consisting of a powdery portion of average particle size between 1 and 250 microns, characterized in that it incorporates anti-caking particles whose average particle size is between 200 and 1500 μm and is at least 2.5 times greater than the average particle size of said powdery part. Its second object is a process for producing a stabilized dry composition, comprising at least one active principle, consisting of a powdery part with an average particle size of between 1 and 250 μm, characterized in that it comprises the step of mixing said powdery portion with anti-caking particles having an average particle size of 200 to 1500 μm and is at least 2.5 times greater than the average particle size of said powdery portion.
Enfin, elle a pour troisième objet l'utilisation d'une composition telle que ci-dessus définie, comme aliment, complément alimentaire ou médicament conditionné sous différentes formes.Finally, its third object is the use of a composition as defined above, as food, dietary supplement or drug packaged in different forms.
De manière surprenante, lorsqu'une composition comprend à la fois une partie pulvérulente de granulométrie comprise entre 1 et 250 μm et des particules antimottantes dont la granulométrie moyenne est comprise entre 200 et 1500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne de la partie pulvérulente, elle ne prend pas en masse et ne subit aucune modification physique ou chimique.Surprisingly, when a composition comprises both a powdery portion with a particle size of between 1 and 250 μm and anti-caking particles whose mean particle size is between 200 and 1500 μm and is at least 2.5 times greater than the grain size distribution. average of the powdery part, it does not take in mass and does not undergo any physical or chemical modification.
L'invention sera mieux comprise a la lecture de la description non limitative qui va suivre .The invention will be better understood on reading the nonlimiting description which follows.
La composition sèche stabilisée selon l'invention comprend au moins un principe actif et est constituée d'une partie pulvérulente et de particules antimottantes qui se distinguent principalement par leur granulométrie. La partie pulvérulente selon l'invention se présente sous la forme d'une poudre fine composée de particules sèches, au moins à leur surface. De façon avantageuse, ladite poudre possède une granulométrie moyenne comprise entre 1 et 250 μm et, plus préférentiellement, entre 10 et 100 μm.The stabilized dry composition according to the invention comprises at least one active principle and is constituted a powdery part and anti-clumping particles which are distinguished mainly by their particle size. The pulverulent part according to the invention is in the form of a fine powder composed of dry particles, at least on their surface. Advantageously, said powder has an average particle size of between 1 and 250 μm and more preferably between 10 and 100 μm.
Selon l'invention, la partie pulvérulente de la composition est présente dans des concentrations allant de préférence de 40% à 95% en poids par rapport au poids total de la composition.According to the invention, the pulverulent portion of the composition is present in concentrations ranging preferably from 40% to 95% by weight relative to the total weight of the composition.
La partie pulvérulente est constituée de principes actifs, d'excipients ou d'un mélange des deux. De manière avantageuse, dans le cadre d'un mélange, la granulométrie moyenne des principes actifs et des excipients sera approximativement identique.The powdery part consists of active ingredients, excipients or a mixture of both. Advantageously, in the context of a mixture, the average particle size of the active ingredients and excipients will be approximately identical.
L'excipient ou le mélange d'excipients susceptibles d'entrer dans la formulation de la partie pulvérulente de la composition selon l'invention sont choisis parmi les sucres tels que le lactose, le saccharose, le dextrose ou les maltodextrines, les sels inorganiques tels que le phosphate dicalcique ou le carbonate de calcium, les acides organiques et leurs sels tels que l'acide citrique, l'acétate de sodium ou le propionate de potassium, les farines végétales et leurs sous-produits tels que la farine de blé, le son, l'amidon de riz ou le gluten maïs, ou leur mélange.The excipient or the mixture of excipients capable of entering into the formulation of the pulverulent part of the composition according to the invention are chosen from sugars such as lactose, sucrose, dextrose or maltodextrins, inorganic salts such as that dicalcium phosphate or calcium carbonate, organic acids and their salts such as citric acid, sodium acetate or potassium propionate, vegetable flours and their by-products such as wheat flour, its, rice starch or gluten corn, or their mixture.
Selon un mode de réalisation avantageux de l'invention, la partie pulvérulente est uniquement constituée de principes actifs.According to an advantageous embodiment of the invention, the pulverulent part consists solely of active principles.
Selon l'invention, les particules antimottantes de l'invention sont également sèches, au moins à leur surface, et se présentent bien souvent sous une forme sphérique, ovoïde ou allongée. Leur surface est lisse, poreuse et/ou creuse et ce, de manière régulière ou irrégulière. De façon avantageuse, les particules antimottantes présentent une granulométrie allant de 200 à 1500 μm, plus préférentiellement de 250 à 800 μm, et encore plus préférentiellement de 300 à 700 μm.According to the invention, the anti-clumping particles of the invention are also dry, at least on their surface, and are often in a spherical, ovoid or elongated form. Their surface is smooth, porous and / or hollow, in a regular or irregular manner. Advantageously, the anti-caking particles have a particle size ranging from 200 to 1500 μm, more preferably from 250 to 800 μm, and even more preferentially from 300 to 700 μm.
Les particules antimottantes de la composition selon l'invention sont constituées de principes actifs, d'excipients ou d'un mélange des deux. Préférentiellement, les principes actifs sont compris, partiellement ou en totalité, dans les particules antimottantes de la composition selon l'invention.The anti-clumping particles of the composition according to the invention consist of active principles, excipients or a mixture of the two. Preferably, the active ingredients are included, partially or totally, in the anti-clumping particles of the composition according to the invention.
De manière préférée, l'excipient ou le mélange d'excipients susceptibles d'entrer dans la composition des particules antimottantes de la composition selon l'invention sont identiques à l'excipient ou au mélange d'excipients entrant dans la composition de la partie pulvérulente .Preferably, the excipient or the mixture of excipients capable of entering into the composition of the anti-clumping particles of the composition according to the invention are identical to the excipient or to the mixture of excipients used in the composition of the powdery part. .
Selon un mode de réalisation avantageux de l'invention, les particules antimottantes de la composition selon l'invention sont des corps simples ou complexes utilisés dans la fabrication ou la préparation d'une composition alimentaire ou médicamenteuse. Il s'agit en particulier de particules de sucres, de mélanges de saccharides, d'acides organiques et leurs sels, de polyols, de sels inorganiques ou de particules creuses à base d'au moins un polymère ou copolymère acrylique ou méthacrylique, pris seuls ou en mélange. A titre d'exemple non limitatif de sucres, on choisira avantageusement le lactose ou le saccharose . A titre d'exemple non limitatif de mélanges de saccharides, on choisira avantageusement les dextrates. A titre d'exemple non limitatif d'acides organiques, on choisira avantageusement l'acide citrique. A titre d'exemple non limitatif de polyols, on choisira avantageusement le mannitol ou le sorbitol. A titre d'exemple non limitatif de sels inorganiques, on choisira avantageusement le phosphate de calcium hydraté. A titre d'exemple non limitatif de particules creuses à base d'au moins un polymère ou copolymère acrylique ou méthacrylique, on choisira avantageusement les , particules de polyméthacrylate .According to an advantageous embodiment of the invention, the anticaking particles of the composition according to the invention are simple or complex bodies used in the manufacture or preparation of a food or drug composition. These are in particular particles of sugars, mixtures of saccharides, organic acids and their salts, polyols, inorganic salts or hollow particles based on at least one acrylic or methacrylic polymer or copolymer, taken alone. or in mixture. As a non-limiting example of sugars, advantageously choose lactose or sucrose. By way of non-limiting example of saccharide mixtures, the dextrates will advantageously be chosen. By way of non-limiting example of organic acids, the citric acid will advantageously be chosen. By way of non-limiting example of polyols, mannitol or sorbitol will advantageously be chosen. As a non-limiting example inorganic salts, the hydrated calcium phosphate is advantageously chosen. By way of nonlimiting example of hollow particles based on at least one acrylic or methacrylic polymer or copolymer, the polymethacrylate particles will advantageously be chosen.
De telles particules antimottantes peuvent avantageusement être obtenues par granulation et par suite se présenter sous la forme de granulés . Une telle granulation peut être effectuée par mélange en milieu humide, et comprendre des étapes de séchage puis de calibrage. Elle peut aussi être réalisée en lit d'air fluidisê ou sur des appareils connus de l'état de la technique combinant un ensemble d'opérations menant aux particules souhaitées, par compactage, par granulation ou par enrobage .Such anti-clumping particles may advantageously be obtained by granulation and consequently be in the form of granules. Such granulation can be carried out by mixing in a humid medium, and include drying and then calibration steps. It can also be carried out in a fluidized air bed or on devices known from the state of the art combining a set of operations leading to the desired particles, by compacting, by granulation or by coating.
Selon l'invention, les particules antimottantes sont présentes dans des concentrations allant de préférence de 5 à 60% en poids par rapport au poids total de la composition et, plus préférentiellement, de 10 à 40%.According to the invention, the anticaking particles are present in concentrations ranging preferably from 5 to 60% by weight relative to the total weight of the composition and, more preferably, from 10 to 40%.
Le principe actif selon l'invention est défini comme tout corps simple ou complexe ayant une activité de n'importe quelle nature sur son environnement. Il vient par définition s'opposer à un excipient qui, simple ou complexe, n'a aucune activité sur l'environnement ou, sur le ou les principes actifs.The active ingredient according to the invention is defined as any simple or complex body having an activity of any nature on its environment. It comes by definition to oppose an excipient which, simple or complex, has no activity on the environment or, on the active principle (s).
Les principes actifs selon l'invention, présents dans la partie pulvérulente et/ou dans les particules antimottantes, sont des corps simples ou complexes choisis parmi les vitamines, les minéraux, les oligoéléments, les acides aminés, les protéines, les enzymes, les facteurs de croissance, les poudres de plantes ou leurs extraits, les inhibiteurs de croissance des insectes, les anti-bactériens, les antifongiques, les antiseptiques, les antibiotiques, les antibiomimétiques, les antiparasitaires et/ou les anti-infectieux de synthèse, pris seuls ou en mélange.The active principles according to the invention, present in the pulverulent part and / or in the anti-caking particles, are simple or complex bodies chosen from vitamins, minerals, trace elements, amino acids, proteins, enzymes, growth powders, plant powders or extracts thereof, insect growth inhibitors, anti-bacterials, antifungals, antiseptics, antibiotics, antibiomimetics, antiparasitic agents and / or synthetic anti-infectives, taken alone or as a mixture.
Le choix d'un principe actif ou d'un mélange de principes actifs tels que décrits précédemment est déterminé par l'utilisation finale de la composition selon l' invention.The choice of an active ingredient or a mixture of active ingredients as described above is determined by the end use of the composition according to the invention.
De manière préférée, la composition sèche stabilisée selon l'invention est un aliment, un complément alimentaire ou un médicament. Les compléments alimentaires sont des produits destinés à être ingérés en compléments de l'alimentation courante, afin de pallier l'insuffisance réelle ou supposée des apports journaliers. Ils contribuent au bon fonctionnement de l'organisme et au bon rétablissement de l'équilibre des différentes fonctions qui l'animent quand celles-ci sont perturbées. Ces compléments alimentaires peuvent se présenter sous la forme de nutraceutiques qui sont des produits fabriqués à partir de produits alimentaires, mais rendu disponible sous forme de comprimé, de poudre, de potion ou d'autres formes médicinales habituellement non associés à des aliments.Preferably, the stabilized dry composition according to the invention is a food, a food supplement or a drug. Food supplements are products intended to be ingested as supplements of the current diet, in order to compensate for the actual or supposed insufficiency of the daily contributions. They contribute to the good functioning of the organism and to the good restoration of the balance of the different functions which animate it when these are disturbed. These dietary supplements may be in the form of nutraceuticals that are products made from food products, but made available as a tablet, powder, potion or other medicinal forms usually not associated with food.
La composition selon l'invention peut comporter en outre, dans sa partie pulvérulente et/ou dans les particules antimottantes, des adjuvants classiques pharmaceutiquement acceptables connus de l'Homme du métier ou des additifs alimentaires tels que des conservateurs, des anti-oxygènes, des acidifiants, des correcteurs d'acidité, des anti-moussants, des émulsifiants, des arômes, des agents appétents, des exhausteurs de goût, des agents moussants, des gélifiants, des humectants, des séquestrants, des stabilisants et des épaississants .The composition according to the invention may further comprise, in its powdery portion and / or in the anti-caking particles, conventional pharmaceutically acceptable adjuvants known to those skilled in the art or food additives such as preservatives, antioxidants, acidifying agents, acid correctors, anti-foaming agents, emulsifiers, flavorings, flavoring agents, flavor enhancers, foaming agents, gelling agents, humectants, sequestering agents, stabilizers and thickeners.
Bien entendu, l'Homme du métier veillera à choisir, de par ses connaissances, le ou les composés à ajouter aux compositions selon l'invention de telle manière que les propriétés avantageuses selon la présente invention ne soient pas ou substantiellement pas altérées.Of course, one skilled in the art will take care to choose, by his knowledge, the compound (s) to be added to the compositions according to the invention in such a way that the advantageous properties according to the present invention are not or not substantially impaired.
La composition selon l'invention résulte par exemple d'un simple mélange mécanique d'une partie pulvérulente contenant des principes actifs et de particules antimottantes tels que décrits ci-dessus. En pratique, elle comporte préférentiellement entre 40 et 95 % m/m (poids du poids total de la composition) de partie pulvérulente et entre 5 et 60 % m/m de particules antimottantes, et, plus préférentiellement, entre 60 et 90 % m/m de principes actifs sous forme pulvérulente et entre 10 et 40 % m/m de particules antimottantes.The composition according to the invention results for example from a simple mechanical mixture of a powdery part containing active ingredients and anti-caking particles as described above. In practice, it preferably comprises between 40 and 95% w / w (weight of the total weight of the composition) of the powdery part and between 5 and 60% w / w of anti-caking particles, and more preferably between 60 and 90% wt. / m of active ingredients in powder form and between 10 and 40% m / m of anti-caking particles.
Préférentiellement, la partie pulvérulente a une granulométrie moyenne comprise entre 20 et 100 μm et les particules antimottantes ont une granulométrie moyenne comprise entre 200 et 800 μm et au moins 2,5 fois supérieure à la granulométrie moyenne de la partie pulvérulente. De manière préférée, la granulométrie moyenne des particules antimottantes est au moins 4 fois supérieure à la granulométrie moyenne de la partie pulvérulente .Preferably, the pulverulent portion has a mean particle size of between 20 and 100 μm and the anti-caking particles have an average particle size of between 200 and 800 μm and at least 2.5 times greater than the average particle size of the powdery part. Preferably, the average particle size of the anti-caking particles is at least 4 times greater than the average particle size of the powdery part.
Par ailleurs, la composition selon l'invention est sèche, c'est-à-dire pas ou peu imprégnée de liquide et, en particulier d'eau. Elle présente préférentiellement une activité de l'eau inférieure à 0,4 et, plus préférentiellement, une activité de l'eau inférieure à 0,3.Furthermore, the composition according to the invention is dry, that is to say not or slightly impregnated with liquid and, in particular water. It preferably has a water activity of less than 0.4 and, more preferably, a water activity of less than 0.3.
En pratique, les compositions selon l'invention ont une date de péremption largement supérieure à la date de péremption que l'on aurait pu obtenir dans des compositions sèches pulvérulentes de l'état de la technique, conservées dans les mêmes conditions.In practice, the compositions according to the invention have an expiry date much greater than the expiry date that could have been obtained in pulverulent dry compositions of the state of the art, preserved under the same conditions.
Le procédé de préparation d'une composition sèche stabilisée selon l'invention est caractérisé en ce qu'il comporte l'étape suivante de mélange de la partie pulvérulente de granulometrie moyenne dont la granulométrie moyenne est comprise entre 200 et 1 500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne dudit principe actif. Cette étape de mélange de la partie pulvérulente avec des particules antimottantes est effectuée selon les techniques habituelles connues.The process for preparing a stabilized dry composition according to the invention is characterized in that it comprises the following step of mixing the part pulverulent medium particle size with an average particle size of between 200 and 1500 microns and is at least 2.5 times greater than the average particle size of said active ingredient. This step of mixing the pulverulent part with anti-caking particles is carried out according to the usual known techniques.
De manière préférée, le procédé de préparation est réalisé dans des conditions d'humidité contrôlées assurant une activité de l'eau inférieure à 0,4 dans la composition obtenue.Preferably, the preparation process is carried out under controlled humidity conditions ensuring a water activity of less than 0.4 in the composition obtained.
L'invention concerne également l'utilisation de la composition selon l'invention comme aliment, comme complément alimentaire, ou comme médicament.The invention also relates to the use of the composition according to the invention as a food, as a food supplement, or as a medicament.
La composition selon l'invention se présente, sous une forme pulvérulente, utilisée en l'état ou destinée à être conditionnée sous différentes formes selon les applications ultérieures . Elle peut avantageusement servir à la fabrication de médicaments à usage humain ou vétérinaire, qui se présentent préférentiellement sous la forme de capsules ou gélules, éventuellement gastrorésistantes, a enveloppe dure ou molle.The composition according to the invention is in a powder form, used in the state or to be packaged in different forms according to the subsequent applications. It can advantageously be used for the manufacture of medicaments for human or veterinary use, which are preferably in the form of capsules or capsules, possibly gastroresistant, hard-coated or soft.
Selon un mode de réalisation avantageux de l'invention, le médicament comprend avantageusement un excipient ou élément de charge de manière à former un prémëlange sous la forme d'une poudre. Préférentiellement, l'excipient ou le mélange d'excipients utilisés pour former ledit prémélange sont identiques à ceux présents dans la partie pulvérulente de la composition selon l'invention. La présente invention va maintenant être illustrée au moyen des exemples suivants .According to an advantageous embodiment of the invention, the medicament advantageously comprises an excipient or a filler element so as to form a premelange in the form of a powder. Preferably, the excipient or the mixture of excipients used to form said premix are identical to those present in the powdery part of the composition according to the invention. The present invention will now be illustrated by the following examples.
Exemple 1 : Composition pulvérulente contenant des extraits de plantes et sa préparation. Constituants Teneur (% m/m)Example 1: Pulverulent composition containing plant extracts and its preparation. Constituents Content (% m / m)
Extraits de plantes absorbés sur 69,00 maltodextrines (Passiflore, Valériane)Extracts of plants absorbed on 69.00 maltodextrins (Passionflower, Valerian)
Sulfate de magnésium 1 , 00 Particules d'acide citrique anhydre 30,00 de 300 à 700 μmMagnesium sulphate 1, 00 Particles of anhydrous citric acid 30.00 from 300 to 700 μm
La composition est préparée en mélangeant les principes actifs sous forme pulvérulente de granulométrie moyenne d'environ 50 μm (extraits de plantes absorbés sur maltodextrines) aux particules d'acide citrique anhydre.The composition is prepared by mixing the active ingredients in pulverulent form with an average particle size of about 50 μm (plant extracts absorbed on maltodextrins) with anhydrous citric acid particles.
Exemple 2 : Composition pulvérulente contenant un mélange d'acides aminés et de vitamines.EXAMPLE 2 Powder Composition Containing a Mixture of Amino Acids and Vitamins
Constituants Teneur (% m/m)Constituents Content (% m / m)
Mélange d'acides aminés et assimilés 22,00Mixture of amino acids and the like 22,00
(lysine, méthionine, chlorure de choline)(lysine, methionine, choline chloride)
Mélange de vitamines lipophiles sur support 33,00Mix of lipophilic vitamins on support 33,00
(vitamines A, D3, E et K3) Mélange de vitamines du groupe B (feed grade (qualité alimentaire) ) 23 , 00(vitamins A, D 3 , E and K 3 ) Vitamin B mixture (feed grade) 23, 00
(vitamines B1, B2, B5, B6, B9, Bi2)(vitamins B 1 , B 2 , B 5 , B 6 , B 9 , Bi 2 )
Vitaminé C 5 , 00Vitamin C 5, 00
Particules de mannitol 17 , 00 La composition est préparée en mélangeant les principes actifs sous forme pulvérulente de granulométrie moyenne d'environ 50 μm (mélange d'acides aminés et de vitamines) aux particules de mannitol de 250 à 800 μm.Mannitol particles 17, 00 The composition is prepared by mixing the active ingredients in powder form of average particle size of about 50 microns (mixture of amino acids and vitamins) with mannitol particles of 250 to 800 microns.
Exemple 3 : Fabrication d'une composition pulvérulente contenant un mélange d'acides aminés et de vitaminesExample 3 Manufacture of a Powder Composition Containing a Mixture of Amino Acids and Vitamins
La composition est préparée en quatre phases : - Phase 1 : le mannitol (76,70%), la crospovidone (3,10%) et la cellulose monocristalline (6,2%) sont granulés en présence d'une solution hydro-alcoolique de povidone (14%) . - Phase 2 : les particules de mannitol obtenues sont séchées puis calibrées pour que leur diamètre moyen soit compris entre 250 μm et 800 μm.The composition is prepared in four phases: Phase 1: mannitol (76.70%), crospovidone (3.10%) and monocrystalline cellulose (6.2%) are granulated in the presence of an aqueous-alcoholic solution of povidone (14%). Phase 2: the mannitol particles obtained are dried and then calibrated so that their mean diameter is between 250 μm and 800 μm.
Phase 3 : les particules de mannitol sont mélangées aux principes actifs sous forme pulvérulente. Phase 4 : la composition obtenue est ensuite conditionnée en sachets aluminisés soudés.Phase 3: the mannitol particles are mixed with the active ingredients in pulverulent form. Phase 4: the composition obtained is then packaged in welded aluminized bags.
Exemple 4 : Etude comparative de la prise en masseExample 4 Comparative Study of Bulking
La présente étude a pour but de comparer la prise en masse de la composition selon l'exemple 1 (composition A) avec une composition B comprenant les mêmes composants que la composition A mais dans laquelle les particules d'acide citrique ont été remplacées par de l'acide citrique en poudre d'une granulométrie faible (voisine de 25 μm) .The purpose of the present study is to compare the setting of the composition according to Example 1 (composition A) with a composition B comprising the same components as composition A, but in which the citric acid particles have been replaced by citric acid powder of a small particle size (close to 25 microns).
Les concentrations des différents constituants des compositions A et B sont reprises ci-dessous :The concentrations of the various constituents of compositions A and B are given below:
Constituants Composition A Composition BConstituents Composition A Composition B
(% m/m) (% m/m)(% m / m) (% m / m)
Mélange d' extraits 69 , 00 69,00Mix of extracts 69, 00 69,00
Sulfate de magnésium 1, 00 1, 00Magnesium sulphate 1, 00 1, 00
Particules d'acide citrique 30,00 0,00 Acide citrique 0 , 00 30,00Particles of citric acid 30.00 0,00 Citric acid 0, 00 30,00
Afin de comparer la prise en masse des deux compositions, on place les différents pots des compositions A et B dans une étuve maintenue à une température de 4O0C et en présence de 75% d'humidité. L'aspect physique des compositions est analysé chaque mois .In order to compare the caking of the two compositions, the various pots of compositions A and B are placed in an oven maintained at a temperature of temperature of 40 ° C. and in the presence of 75% humidity. The physical aspect of the compositions is analyzed each month.
Les résultats expérimentaux sont repris dans le tableau ci-dessous :The experimental results are shown in the table below:
Ces résultats montrent que la composition A ne présente pas de prise en masse contrairement à la composition B. En conséquence, il semble que le remplacement de l'acide citrique en poudre d'une granulométrie voisine de 25 μm. (composition B) par des particules d'acide citrique présentant une granulométrie comprise entre 300 μm et 700μm (composition A) a pour effet de supprimer la prise en masse et ainsi d'améliorer la stabilité de la composition selon l'invention.These results show that composition A does not have a setting in mass contrary to composition B. As a result, it seems that the replacement of citric acid powder with a particle size of about 25 microns. (composition B) with citric acid particles having a particle size of between 300 .mu.m and 700 .mu.m (composition A) has the effect of suppressing the setting of mass and thus improve the stability of the composition according to the invention.
En outre, compte tenu du fait qu'une semaine de conservation dans les conditions opératoires du présent exemple équivaut à environ 3 mois de conservation à 250C, il est permis de conclure qu'une composition selon l'invention telle que la composition A, conservée à des températures de l'ordre de 250C, devrait présenter une péremption au cours du temps nettement améliorée par rapport à des compositions substantiellement exemptes de particules . In addition, considering that a week of storage under the operating conditions of the present example is equivalent to about 3 months of storage at 25 ° C., it can be concluded that a composition according to the invention such as composition A , kept at temperatures of the order of 25 0 C, should have a significantly improved shelf life over substantially non-particulate compositions.

Claims

REVENDICATIONS
1. Composition sèche stabilisée, comprenant au moins un principe actif, constituée d'une partie pulvérulente de granulometrie moyenne comprise entre 1 et 250 μm, caractérisée en ce qu'elle incorpore des particules antimottantes dont la granulométrie moyenne est comprise entre 200 et 1500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne de ladite partie pulvérulente.1. Stabilized dry composition, comprising at least one active ingredient, consisting of a powdery portion having an average particle size of between 1 and 250 μm, characterized in that it incorporates anti-caking particles whose mean particle size is between 200 and 1500 μm. and is at least 2.5 times greater than the average particle size of said powdery portion.
2. Composition sèche stabilisée selon la revendication 1, caractérisée en ce que la granulométrie moyenne des particules antimottantes est au moins 4 fois supérieure à la granulométrie moyenne de ladite partie pulvérulente .2. stabilized dry composition according to claim 1, characterized in that the average particle size of the anti-caking particles is at least 4 times greater than the average particle size of said powdery portion.
3. Composition sèche stabilisée selon l'une quelconque des revendications 1 ou 2, caractérisée en ce qu'elle comprend entre 5 et 60% m/m, préférentiellement , entre 10 et 40% m/m de particules antimottantes.3. Stabilized dry composition according to any one of claims 1 or 2, characterized in that it comprises between 5 and 60% w / w, preferably between 10 and 40% w / w of anti-clumping particles.
4. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce que les particules antimottantes sont choisies parmi les sucres, les mélanges de saccharides, les acides organiques et leurs sels, les polyols, les sels inorganiques ou les particules creuses à base d'au moins un polymère ou copolymère acrylique ou méthacrylique, pris seuls ou en mélange.4. Stabilized dry composition according to any one of the preceding claims, characterized in that the anti-caking particles are chosen from sugars, saccharide mixtures, organic acids and their salts, polyols, inorganic salts or hollow particles. base of at least one acrylic or methacrylic polymer or copolymer, alone or as a mixture.
5. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce que les particules antimottantes sont poreuses et/ou creuses . 5. Stabilized dry composition according to any one of the preceding claims, characterized in that the anti-caking particles are porous and / or hollow.
6. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce que la partie pulvérulente est uniquement constituée de principes actifs.6. Stabilized dry composition according to any one of the preceding claims, characterized in that the pulverulent portion consists solely of active ingredients.
7. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce que les principes actifs sont compris, partiellement ou en totalité, dans les particules antimottantes .7. stabilized dry composition according to any one of the preceding claims, characterized in that the active ingredients are included, partially or in whole, in the anti-caking particles.
8. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce que les principes actifs sont choisis parmi les vitamines, les minéraux, les oligo-éléments, les acides aminés, les protéines, les enzymes, les facteurs de croissance, les poudres de plantes et leurs extraits, les inhibiteurs de croissance des insectes, les antibactériens, les antifongiques, les antiseptiques, les antibiotiques, les antibiomimétiques, les antiparasitaires et/ou les anti-infectieux de synthèse, pris seuls ou en mélange .8. Stabilized dry composition according to any one of the preceding claims, characterized in that the active ingredients are selected from vitamins, minerals, trace elements, amino acids, proteins, enzymes, growth factors, plant powders and extracts thereof, insect growth inhibitors, antibacterials, antifungals, antiseptics, antibiotics, antibiomimetics, antiparasitics and / or synthetic anti-infectives, alone or as a mixture.
9. Composition sèche stabilisée selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle présente une activité de l'eau inférieure à 0,4.9. stabilized dry composition according to any one of the preceding claims, characterized in that it has a water activity of less than 0.4.
10. Procédé de fabrication d'une composition sèche stabilisée, comprenant au moins un principe actif, constituée d'une partie pulvérulente de granulométrie moyenne comprise entre 1 et 250 μm, caractérisé en ce qu'il comporte l'étape de mélange de ladite partie pulvérulente avec des particules antimottantes dont la granulométrie moyenne est comprise entre 200 et 1 500 μm et est au moins 2,5 fois supérieure à la granulométrie moyenne de ladite partie pulvérulente.10. Process for the manufacture of a stabilized dry composition, comprising at least one active principle, consisting of a powdery part with a mean particle size of between 1 and 250 μm, characterized in that it comprises the step of mixing said part. powder with anti-clumping particles whose mean particle size is between 200 and 1500 μm and is at least 2.5 times greater than the average particle size of said powdery portion.
11. Procédé selon la revendication 10, caractérisé en ce qu'il est réalisé dans des conditions d'humidité contrôlées assurant une activité de l'eau inférieure à 0,4 dans la composition obtenue.11. The method of claim 10, characterized in that it is carried out under controlled humidity conditions ensuring a water activity of less than 0.4 in the composition obtained.
12.Utilisation de la composition sèche stabilisée selon l'une quelconque des revendications 1 à 9 pour la préparation d'un aliment.12.Use of the stabilized dry composition according to any one of claims 1 to 9 for the preparation of a food.
13.Utilisation de la composition sèche stabilisée selon l'une quelconque des revendications 1 à 9 pour la préparation d'un complément alimentaire13.Use of the stabilized dry composition according to any one of claims 1 to 9 for the preparation of a dietary supplement
14.Utilisation de la composition sèche stabilisée selon l'une quelconque des revendications 1 à 9 pour la préparation d'un médicament à usage humain ou vétérinaire.14.Use of the stabilized dry composition according to any one of claims 1 to 9 for the preparation of a medicament for human or veterinary use.
15.Médicament caractérisé en ce qu'il comprend la composition sèche stabilisée selon l'une quelconque des revendications 1 à 9.15. A medicament characterized in that it comprises the stabilized dry composition according to any one of claims 1 to 9.
16.Médicament selon la revendication 15 caractérisé en ce qu'il se présente sous la forme de gélules ou de poudres . 16. Medicament according to claim 15 characterized in that it is in the form of capsules or powders.
EP06831040A 2005-11-02 2006-10-31 Stabilized dry compositions, method for obtaining them and use thereof Revoked EP1945341B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0511148A FR2892643B1 (en) 2005-11-02 2005-11-02 STABILIZED DRY COMPOSITIONS, PROCESSES FOR THEIR PREPARATION AND USES THEREOF
PCT/FR2006/002428 WO2007051918A1 (en) 2005-11-02 2006-10-31 Stabilized dry compositions, method for obtaining them and use thereof

Publications (2)

Publication Number Publication Date
EP1945341A1 true EP1945341A1 (en) 2008-07-23
EP1945341B1 EP1945341B1 (en) 2009-12-23

Family

ID=36685902

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06831040A Revoked EP1945341B1 (en) 2005-11-02 2006-10-31 Stabilized dry compositions, method for obtaining them and use thereof

Country Status (7)

Country Link
EP (1) EP1945341B1 (en)
AT (1) ATE452700T1 (en)
BR (1) BRPI0614816A2 (en)
DE (1) DE602006011355D1 (en)
ES (1) ES2335142T3 (en)
FR (1) FR2892643B1 (en)
WO (1) WO2007051918A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018233949A1 (en) * 2017-06-19 2018-12-27 Lanxess Deutschland Gmbh Mixtures for the adsorption of acidic gases

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3367883A (en) * 1961-10-17 1968-02-06 Monsanto Co Processes and products for conditioning caking salts
GB973293A (en) * 1962-01-11 1964-10-21 Sternol Ltd A new or improved freely flowing powder
GB1168106A (en) * 1967-08-30 1969-10-22 English Clays Lovering Pochin Improvements in or relating to Granular Materials containing Anti-Caking Powders
DE2217386A1 (en) * 1972-04-11 1972-12-14 Kewanee Oil Co , Bryn Mawr, Pa (V St A) Non-dusting pigments - by mixing with finely divided ptfe and liquid processing auxiliary
FR2863914B1 (en) * 2003-12-22 2006-05-26 Rhodia Chimie Sa USE OF ADIPIC ACID AS A MILLING AGENT IN DRY GRINDING MINERAL MATERIALS

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007051918A1 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018233949A1 (en) * 2017-06-19 2018-12-27 Lanxess Deutschland Gmbh Mixtures for the adsorption of acidic gases
US11207671B2 (en) 2017-06-19 2021-12-28 Lanxess Deutschland Gmbh Mixtures for the adsorption of acidic gases

Also Published As

Publication number Publication date
WO2007051918A1 (en) 2007-05-10
DE602006011355D1 (en) 2010-02-04
EP1945341B1 (en) 2009-12-23
FR2892643B1 (en) 2007-12-21
BRPI0614816A2 (en) 2011-04-12
FR2892643A1 (en) 2007-05-04
ES2335142T3 (en) 2010-03-22
ATE452700T1 (en) 2010-01-15

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